Automated Synthesis of [11C]acetoacetate on a commercially available synthesizer with non-human pirmate PET brain imaging

403 Objectives Current strategies to assess brain metabolism using [18F]FDG provide no information regarding the brain’s innate ability to use ketone bodies. As the main fuel alternate to glucose, ketones can account for up to 60% of brain metabolic demands in order to help mitigate states of decreased glucose metabolism that are observed in conditions such as Alzheimer’s disease (AD). Recent studies show that cognitive function can be significantly improved in memory impaired adults by ketogenic dietary intervention (Neurobiology of Aging 2012, 33(2)425). PET imaging using [11C]acetoacetate provides real time biochemical analysis of brain fuel utilization that can help uncover the role of ketone metabolism in early AD and potentially lead to new preventive and therapeutic strategies (Neurobiol Aging. 2014;35(6):1386-95). Here, we report for the first time the automated synthesis [11C]acetoacetate in a commercially available radiochemistry synthesizer (TRASIS AllInOne) and report its utility in Non-Human Primate (NHP) brain. Methods [11C]acetoacetate was optimized and automated in a TRASIS AIO module with slight modifications from previously published synthesis (Appl Radiat Isot. 2007 65(8):934-40). Briefly, the one-pot synthesis was carried out by [11C]carboxylation of the corresponding enolate anion generated in situ from isopropenylacetate and MeLi and further purified by trapping the radiotracer on ion-exchange column resins and eluting with citrate buffer. PET imaging studies were conducted on the same day on adult vervet monkeys after the administration of [11C]acetoacetate. Results [11C]acetoacetate was synthesized with high radiochemical purity (>95%) and specific activity (~1800 mCi/µmol, n >10) with 40% radiochemical yield, decay corrected to EOS. The total time required for the synthesis, including [11C]CO2 production, radiolabelling, purification and formulation was ~16 min. Furthermore, the uptake kinetics in NHP brain was similar to what was reported in humans (Neurobiol Aging. 2014 Jun;35(6):1386-95) Conclusions The automated radiolabeling procedure for [11C]acetoacetate that we demonstrate here on a widely available radiochemistry synthesizer can be easily adapted to any commercially available automated module for human injections. In addition, we demonstrate for the first time the uptake and clearance pattern of [11C]acetoacetate in a NHP brain is similar to the pattern observed in humans, opening up the possibility of using [11C]acetoacetate PET to address questions of alternate brain energy metabolism in NHP models of human diseases.